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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1991-08-26 to 1991-10-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection 1990-05-14

Test material

Constituent 1
Chemical structure
Reference substance name:
Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., calcium salts (2:1)
EC Number:
931-276-9
Cas Number:
114959-46-5
Molecular formula:
See information in Section 1.2.
IUPAC Name:
Benzoic acid, 2-hydroxy-, mono-C14-18-alkyl derivs., calcium salts (2:1)
Details on test material:
- Name of test material (as cited in study report): [CAS Number 114959-46-5]
- Physical state: Clear brown viscous liquid
- Lot/batch No.: 191 (Stanlow); DSP4767/91
- Toxicology reference number: ST91/247
- Stability under test conditions: Stable for the duration of the study under the test conditions employed
- Storage condition of test material: In the dark at ambient temperature under nitrogen
- Date received: 08 August 1991

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Froxfield Farms UK Ltd
- Age at study initiation: 3 to 5 months
- Weight at study initiation: 3.38-4.38 kg (males); 3.42-4.506 kg (females)
- Fasting period before study:
- Housing: Singly in hanging, stainless steel cages with perforated dimple or wire-mesh flooring. Sawdust-filled undertrays for excreta were placed beneath each cage and changed twice weekly. Each cage measured 91 cm x 66 cm x 45 cm.
- Diet (e.g. ad libitum): Pelleted diet (Standard Rabbit Diet, SQC, Special Diet Services Ltd) ad libitum
- Water (e.g. ad libitum): Water from the public supply ad libitum
- Acclimation period: At least two weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 15-20 degrees Centigrade with animal room temperature exceeding the target range by up to 0.3 degrees Centigrade on five days. However, these excusions had no apparent effect on the health of the animals.
- Humidity: 30-70 % with animal room humidity exceeding the target range for more than two consecutive (4-hourly) recordings on eight days of the study. However, these excusions had no apparent effect on the health of the animals.
- Photoperiod: 12 hour day and 12 hour night provided by automatically controlled fluorescent lighting

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL of undiluted test material
Duration of treatment / exposure:
Single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
3 males and 3 females
Details on study design:
Animals with eyes free from irritation, occular defects or corneal injury were used. The undiluted test material was placed into the lower conjunctival sac of one eye of each animal. The treated eye was gently held closed for a few seconds to prevent loss of the test material. The eyes were not irrigated.

The immediate reactions of the rabbits were scored as an initial pain response using a six point scale (see Attachment A). Other ocular reactions to treatment were noted and scored using standard grades (see Attachment A). The mean scores at each time point and the group mean scores at 24, 48 and 72 hours were calculated.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
animal: 479M
Time point:
other: 1 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal: 479M
Time point:
other: 4 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal: 479M
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal: 479M
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Basis:
animal: 479M
Time point:
72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal: 479M
Time point:
other: 1h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal: 479M
Time point:
other: 4 h
Score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
animal: 479M
Time point:
24 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal: 479M
Time point:
48 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
animal: 479M
Time point:
72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 479M
Time point:
other: 1h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 479M
Time point:
other: 4h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 479M
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: 479M
Time point:
other: 1h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: 479M
Time point:
other: 4 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
animal: 479M
Time point:
24/48/72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 539M
Time point:
other: 1 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 539M
Time point:
other: 4 h
Score:
2
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: 539M
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 539M
Time point:
48 h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 539M
Time point:
72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 539M
Time point:
other: 1h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: 539M
Time point:
other: 4h
Score:
2
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: 539M
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: 539M
Time point:
48 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 539M
Time point:
72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 539M
Time point:
other: 1h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 539M
Time point:
other: 4h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 539M
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 539M
Time point:
other: 1h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 539M
Time point:
other: 4h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 539M
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 540M
Time point:
other: 1h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 540M
Time point:
other: 4h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 540M
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 540M
Time point:
48 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 540M
Time point:
72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 540M
Time point:
other: 1h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 540M
Time point:
other: 4h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: 540M
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 540M
Time point:
other: 1h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 540M
Time point:
other: 4h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 540M
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 540M
Time point:
other: 1h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 540M
Time point:
other: 4h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 540M
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 544F
Time point:
other: 1h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 544F
Time point:
other: 4h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 544F
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 544F
Time point:
48 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 544F
Time point:
72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 544F
Time point:
other: 1h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 544F
Time point:
other: 4h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 544F
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 544F
Time point:
other: 1h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 544F
Time point:
other: 4h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 544F
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 544F
Time point:
other: 1h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 544F
Time point:
other: 4h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 544F
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 545F
Time point:
other: 1h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 545F
Time point:
other: 4h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 545F
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 545F
Time point:
48 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 545F
Time point:
72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 545F
Time point:
other: 1h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 545F
Time point:
other: 4h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 545F
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 545F
Time point:
other: 1h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 545F
Time point:
other: 4h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 545F
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 545F
Time point:
other: 1h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 545F
Time point:
other: 4h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 545F
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 546F
Time point:
other: 1h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 546F
Time point:
other: 4h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 546F
Time point:
24 h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
conjunctivae score
Basis:
animal: 546F
Time point:
48 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal: 546F
Time point:
72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 546F
Time point:
other: 1h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 546F
Time point:
other: 4h
Score:
1
Reversibility:
fully reversible within: 72h
Irritation parameter:
chemosis score
Basis:
animal: 546F
Time point:
24 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 546F
Time point:
48 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal: 546F
Time point:
72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 546F
Time point:
other: 1h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 546F
Time point:
other: 4h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal: 546F
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 546F
Time point:
other: 1h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 546F
Time point:
other: 4h
Score:
0
Irritation parameter:
iris score
Basis:
animal: 546F
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
There was no initial pain response upon administration of the test material. Conjunctival reactions to ocular instillation of the test material did not exceed a crimson-red appearance, chemosis causing partial eversion of the eyelids and a slight ocular discharge. Such reactions resolved within 48 hours (chemosis) and 72 hours (redness) of treatment. The cornea and iris remained overtly unaffected by the test material.
Other effects:
No data

Applicant's summary and conclusion

Conclusions:
There was no initial pain response upon administration of the test substance. Single instillation of the undiluted test material into one ocular sac of each of six rabbits caused conjunctival irritation that resolved within 72 hours of treatment. The most intense irritation reactions did not exceed a crimson red appearance, chemosis causing partial eversion of the eyelids and slight ocular discharge.